This program will explore in detail the pharmacological consequences of abuse of the various classes of drugs which are of social concern. Earlier studies in our laboratories, as well as others, have indicated that monkeys will not self-administer delta 9 (THC). However, when large doses are administered systematically, a mild form of physiological dependence develops. The dose required to produce this phenomenon is larger than that which would ordinarily be ingested by smoking marihuana. An electrolyte imbalance is associated with the barbiturate withdrawal syndrome. The hormonal mediation of this phenomena will be studied. The disruption of the menstrual cycle by chronic narcotic ingestion has been confirmed in the monkey in our laboratories. The ovulation-related estrogen peak at mid-cycle is absent. The apparent lack of ovulation will be confirmed by assaying for Luteinizing Hormone. Various forms of physiological dependence develop upon the chronic administration of centrally-acting depressant drugs. Acute pharmacological effect of these drugs and the withdrawal effects of these drugs have not been monitered. Some of these pharmacological effects must reinforce behavior. To date, there has been no experimental evidence relating to changes in vital signs which occur during administration of drugs of abuse to the intact waking subject. Actonomic Nervous System effects will be explored to establish correlation with behavioral effects.